Tricyclic antidepressant agents such as nortriptyline, imipramine, etc., are widely used in psychiatric practice. Unfortunately, a major risk in treating depressed patients with a tricyclic antidepressant agent (TCA) is that of prescribing a potentially toxic drug to individuals who are likely to attempt suicide by ingesting an overdosage. Cardiotoxicity represent the most serious of the complications of TCA poisoning; unfortunately, considerable uncertainty and controversy exists as to the proper clinical management of this life-threatening entity. This is related to the absence of systematic well controlled investigations on the use and effectiveness of various potential antidotes for TCA intoxication. The aim of this project is to study the problem in animals under controlled laboratory conditions so that the clinical management of a life-threatening entity can be performed on a scientifically sound basis. This will be accomplished by studies designed to (1) characterize TCA-induced toxicity in several animal species, (2) screen a variety of agents for effectiveness as antidotes against TCA-induced cardiotoxicity and (3) determine the mechanism of protection produced by antidotes.